Research Papers:

Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma

Anna Maria Rachiglio, Riziero Esposito Abate, Alessandra Sacco, Raffaella Pasquale, Francesca Fenizia, Matilde Lambiase, Alessandro Morabito, Agnese Montanino, Gaetano Rocco, Carmen Romano, Anna Nappi, Rosario Vincenzo Iaffaioli, Fabiana Tatangelo, Gerardo Botti, Fortunato Ciardiello, Monica R. Maiello, Antonella De Luca and Nicola Normanno _

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Oncotarget. 2016; 7:66595-66605. https://doi.org/10.18632/oncotarget.10704

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Anna Maria Rachiglio1, Riziero Esposito Abate1, Alessandra Sacco1, Raffaella Pasquale1, Francesca Fenizia1, Matilde Lambiase1, Alessandro Morabito2, Agnese Montanino2, Gaetano Rocco3, Carmen Romano4, Anna Nappi4, Rosario Vincenzo Iaffaioli4, Fabiana Tatangelo5, Gerardo Botti5, Fortunato Ciardiello6, Monica R. Maiello7, Antonella De Luca7, Nicola Normanno1,7

1Laboratory of Pharmacogenomics, CROM-Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

2Thoraco-Pulmonary, Medical Oncology, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

3Thoracic Surgery, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

4Gastro-Intestinal Medical Oncology, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

5Surgical Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

6Department of Clinical and Experimental Medicine ‘F. Magrassi’-Medical Oncology, Seconda Università degli Studi di Napoli, Napoli, Italy

7Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy

Correspondence to:

Nicola Normanno, email: [email protected], [email protected]

Keywords: targeted sequencing, colon cancer, lung cancer, liquid biopsy, driver mutations

Received: April 26, 2016     Accepted: May 29, 2016     Published: July 19, 2016


The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from EGFR-mutant NSCLC patients (sensitivity 77.3%). The concordance rate between tissue and plasma in NSCLC was much lower for other mutations such as KRAS that, based on the allelic frequency and the fraction of neoplastic cells, were likely to be sub-clonal. NGS also identified EGFR mutations in plasma samples from two patients with EGFR wild type tumor tissue. Both mutations were confirmed by droplet digital PCR (ddPCR) in both plasma and tissue samples. In CRC, the sensitivity of the NGS plasma analysis for RAS mutations was 100% (6/6) in patients that had not resection of the primary tumor before blood drawing, and 46.2% (6/13) in patients with primary tumor resected before enrollment. Our study showed that NGS is a suitable method for plasma testing. However, its clinical sensitivity is significantly affected by the presence of the primary tumor and by the heterogeneity of driver mutations.

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PII: 10704